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T. Landberg et al. / Medical Physics in the Baltic States 7 (2009) 43 - 51 high “relative seriality”, implying that a dose above tolerance limit to even a small volume of the Organ at Risk may be deleterious, whereas the lung usually has a low “relative seriality”, meaning that it may be the relative size of the volume that is irradiated above tolerance level that is the most important parameter. As an example can be mentioned late effects from mantle treatment for Hodgkin´s disease. The late effects from the (partial) irradiation of the lungs (a parallel tissue) were much less serious than those from the heart (a combined serial [coronary arteries] and parallel [myocardium] tissue). For the moment the model has not been tested enough to allow for firm recommendations, but indeed it highlights an important problem. Fig. 3. Schematic examples of tissue organization structures in the parallel-serial model. a) a serial string of subunits (e.g., the spinal cord), b) a parallel string of subunits (e.g., the lungs), c) a serial-parallel string of subunits (e.g., the heart), d) a combination of parallel and serial structures (e.g., a nephron). Modified from Withers et al., (1988) and Källman et al., (1992). It may be useful to state whether the Organ at Risk is considered to be arranged mainly Serially ("Se"), mainly in Parallel ("Pa"), or mainly in a serial-parallel mixed fashion (“Mi”). Planning Organ at Risk Volume (PRV) As is the case with the Planning Target Volume, any movements of the Organ(s) at Risk during treatment, as well as uncertainties in the set-up during the whole treatment course must be considered. An integrated margin has to be added to the OR to compensate for these variations and uncertainties, using the same principles of Internal and Set-up Margins as for the PTV. This leads, in analogy with the PTV, to the concept of Planning Organ at Risk Volume (PRV). Note that a PTV and a PRV may overlap. Treated Volume. Due to the limitations of the irradiation techniques and in some specific clinical situations, the volume receiving the prescribed dose may not match accurately the PTV; it may be larger (sometimes much larger) and in general 47 of a simpler shape. This leads to the concept of Treated Volume. It is defined when the treatment planning procedure is completed and the beam arrangement as well as all the other irradiation parameters have been selected. The Treated Volume is the tissue volume which (according to the approved treatment plan) is planned to receive at least a dose selected and specified by the radiation oncologist as being appropriate to achieve the purpose of the treatment, e.g. tumor eradication, or palliation. The treated volume is thus a volume enclosed by the isodose surface corresponding to that dose level. For example, if the prescribed dose is 60 Gy, and the minimum dose (considered to be adequate) was 5 % below the central dose (which was normalized to 100 %), the treated volume is then enclosed by the 57 Gy isodose surface. Normally, in the patient, the tissue volume which actually receives that dose level (i.e. "actual" treated volume) should match the "planned" treated volume (“Conformal Therapy”). It is important to identify the Treated Volume and its shape, size, and position in relation to the PTV for different reasons. One is to evaluate causes for local recurrences ("infield" [=too low dose] versus "marginal" [=too small volume] ones). An other is to evaluate complications in normal tissues encountered outside the PTV but within the Treated Volume. The comparison of the Treated Volume and the PTV for different beam arrangements can be used as part of the optimization procedure ("conformity index”). Irradiated Volume The Irradiated Volume is the tissue volume which receives a dose that is considered significant in relation to normal tissue tolerance. If the Irradiated Volume is reported, the significant dose must be expressed either in absolute values (in Gy) or relative to the specified dose to the PTV. The Irradiated Volume depends on the treatment technique used. Probability of Benefit versus Risk of Complications It is recognized that the linear addition of the margins for all types of uncertainties would generally lead to an excessively large PTV. This could result in exceeding the patient tolerance and fail to reflect the actual clinical consequences. The risk of missing part of the cancer cell population must be balanced against the reduction of the risk of severe and serious normal tissue complications. The balance between disease control and risk of complications often dictates acceptance of reduced probability of cure in order to avoid severe and serious treatment-related complications. Therefore, the selection of a composite margin and the delineation of the border of the PTV involve a compromise that relies upon the experience and the judgment of the radiation-oncology team. Colour Code.
T. Landberg et al. / Medical Physics in the Baltic States 7 (2009) 43 - 51 For each volume defined, a color code is proposed to assure clarity of interpretation. GTV: Gross Tumor Volume (dark red) CTV: Clinical Target Volume (pink) ITV: Internal Target Volume (dark blue) PTV: Planning Target Volume (light blue) OR: Organ at Risk (dark green) PRV: Planning Organ at Risk Volume (light green) Landmarks (black) Fig. 4. Schematic representation of the different volumes/margins. Note: (1) The Internal Margin may be asymmetrical. (2) Like the Internal Margin, the Set-up Margin may also be asymmetrical. (3) To delineate the PTV, the IM and SM are not added linearly (since this could result in an excessively large PTV), but are combined (for explanation, see text). The PTV is thus smaller than if one would simply have added the IM and SM linearly. (4) For Organs at Risk (OR), margins are added in the same way as for the PTV. (5) The PTV and PRV may or may not overlap. Note that when the Treated Volume is made smaller by use of many beams (e.g. in IMRT) the Irradiated Volume gets larger. Scenario A. A margin is added around the Gross Tumor Volume (GTV) to take into account potential “subclinical“ invasion. The GTV and this margin define the Clinical Target Volume (CTV). In external beam therapy, to ensure that all parts of the CTV receive the prescribed dose, additional safety margins for geometric variations and uncertainties must be considered. 48 An Internal Margin (IM) is added for the variations in position and/or shape and size of the CTV. This defines the Internal Target Volume. A Set-up Margin (SM) is added to take into account all the variations/uncertainties in patient-beam positioning. The CTV combined with the IM and the SM define the Planning Target Volume (PTV) on which the selection of beam size and arrangement is based. Fig. 5. Schematic representations of the relations between the different volumes (GTV, CTV, PTV, and PRV) in different clinical scenarios. Scenario B. The simple (linear) addition of all factors of geometric uncertainty, as indicated in scenario A, often leads to an excessively large PTV, which would be incompatible with the tolerance of the surrounding normal tissues. In such instances, instead of adding linearly the Internal Margin and the Set Up Margin, compromise 2 combinations are used, e.g., ∑ σ formalism. This quantitative evaluation is only relevant if all uncertainties, and their σ, are known, i.e. in a few sophisticated protocols. Scenario C. In the majority of the clinical situations, a “global“ safety margin is adopted. In some cases, the presence of Organs at Risk dramatically reduces the width of the acceptable safety margin (e.g., presence of the spinal cord, optical nerve, etc.). In other situations, larger safety margins may be accepted. Since the incidence of subclinical invasion may decrease with distance from the GTV, a reduction of the margin for subclinical invasion may still be compatible with chance for cure, albeit at a lower probability rate. It is important to stress that the thickness of the different safety margins may vary with the angle from which one looks at the PTV (e.g., bony structures or
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